The invention relates to immortalized hepatocyte cell lines.
Hybrid extracorporeal liver assist devices (LAD) are a promising therapeutic modality to reduce the potential of hepatic encephalopathy (HE) in patients-with fulminant hepatic failure (FHF) (Sussman et al., 1995, Sci. Am. Science & Medicine May/June 1995:68-77). The exact identity of the toxic metabolites responsible for HE are not clear, but benzodiazepine-like compounds and ammonia have been implicated. The metabolism of benzodiazepines in liver is accomplished by liver-specific cytochrome P450 enzymes.
Two cell based liver support systems have undergone clinical trials in hepatic failure patients. The first device (Sussman et al., 1994, Artif. Organs 18:390-396) contains the cell line C3A (Kelly, J H, WO91/18087) which was subcloned from the hepatoma cell line Hep G2 (Knowles et al., U.S. Pat. No. 4,393,133). The Hep G2/C3A cell line reportedly is tumorigenic. The second device incorporates freshly isolated porcine hepatocytes (Rozga et al., 1994, Ann. Surg. 219: 538-546).
In a study comparing primary hepatocytes to HepG2 cells, the primary cells were superior to the transformed cell in every biotransformation pathway assessed (Nyberg et al., 1994, Ann. Surg. 220:59-67), but primary hepatocytes only transiently provide metabolic functions. Many metabolic activities are rapidly lost in culture.